A novel negative checkpoint regulator designated V-domain Ig Suppressor of T cell Activation (VISTA) is a newly identified Ig domain-containing immune-checkpoint molecule that directly suppresses T-cell activation in vitro and in vivo. The human and murine VISTA / B7-H5 / GI24 proteins share 90% identity and display similar expression patterns. VISTA / B7-H5 / GI24 is constitutively expressed within the hematopoietic compartment, with the highest expression level on myeloid cells and a lower level on CD4+, CD8+ T cells, and Foxp3+CD4+ regulatory T cells. A soluble VISTA-Ig protein that contains the extracellular domain fused with Ig-crystalizable fragment (Fc) or full-length VISTA / B7-H5 / GI24 expressed on APCs acts as a ligand to suppress T-cell proliferation and cytokine production. In addition, VISTA / B7-H5 / GI24 might function as an inhibitory receptor on T cells to suppress their activation . VISTA / B7-H5 / GI24-specific monoclonal antibody (mAb) enhances disease severity in the experimental autoimmune encephalomyelitis (EAE) model, as well as boosts antitumor immunity in multiple murine tumor models.
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